The human colon is colonised with a wide range of bacteria that have both positive and negative effects on gut physiology as well as having other systemic influences. Predominant groups of bacteria found in the colon include bacteroides, bifidobacteria, eubacteria, clostridia and lactobacilli. The bacteria present have fluctuating activities in response to substrate availability, redox potential, pH, O2 tension and distribution in the colon. In general intestinal bacteria can be divided into species that exert either potentially harmful or beneficial effects on the host. Pathogenic effects (which may be caused by clostridia or bacteroides, for example) include diarrhoea, infections, liver damage, carcinogenesis and intestinal putrefaction. Health-promoting effects may be caused by the inhibition of growth of harmful bacteria, stimulation of immune functions, improving digestion and absorption of essential nutrients and synthesis of vitamins. An increase in numbers and/or activities of bacterial groups (such as Bifidobacterium and Lactobacillus) that may have health promoting properties is desirable.
As far as infants specifically are concerned, immediately before birth, the gastro-intestinal tract of a baby is thought to be sterile. During the process of birth, it encounters bacteria from the digestive tract and skin of the mother and starts to become colonised. Large differences exist with respect to the composition of the gut microbiota in response to the infant's feeding. The faecal flora of breast-fed infants includes appreciable populations of Bifidobacteria with some Lactobacillus species, whereas formula-fed infants have more complex microbiota, with Bifidobacteria, Bacteroides, Clostridia and Streptococci all usually present. After weaning, a pattern of gut microbiota that resembles the adult pattern becomes established.
One approach to promote the numbers and/or activities of beneficial bacteria in the colon is the addition of prebiotics to foodstuffs. A prebiotic is a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Such ingredients are non-digestible in the sense that they are not broken down and absorbed in the stomach or small intestine and thus pass intact to the colon where they are selectively fermented by the beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS).
Human milk is known to contain a larger amount of indigestible oligosaccharides than most other animal milks. In fact, indigestible oligosaccharides represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 12-15 g/l in colostrum and 5-8 g/l in mature milk. Human milk oligosaccharides are very resistant to enzymatic hydrolysis, indicating that these oligosaccharides may display essential functions not directly related to their calorific value.
Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Infant formulas have been developed for these situations. As the composition of human milk becomes better understood, it has also been proposed to add prebiotics to infant formula. Various infant formulas supplemented with prebiotics such as mixtures of fructooligosaccharides and galactooligosaccharides for example are commercially available. However, such mixtures approximate only roughly the mixture of oligosaccharides in human milk. Over 100 different oligosaccharide components have been detected in human milk some of which have not been so far detected in animal milks such as bovine milk at all or have been detected only in small quantities. Examples of classes of human milk oligosaccharide that are present in bovine milk and colostrum only in very small quantities or not at all are sialylated and fucosylated oligosaccharides.
US Patent Application No. 2003/0129278 describes an oligosaccharide mixture based on oligosaccharides produced from one or several animal milks which is characterized in that it comprises at least two oligosaccharide fractions which are each composed of at least two different oligosaccharides, with free lactose not pertaining thereto. The total spectrum of the oligosaccharides present in the oligosaccharide mixture differs from those present in the animal milk or animal milks from which the oligosaccharide fractions were extracted. Further a) if said oligosaccharides are extracted from only one animal milk, the proportion of neutral oligosaccharides to acidic (sialylated) oligosaccharides is 90-60: 10-40 weight %, or b) if said oligosaccharides are extracted from at least two animal milks, the oligosaccharides extracted from two different animal milks each make up 10 weight % of the total amount of oligosaccharides present in the oligosaccharide mixture.
WO2007/090894 describes an oligosaccharide mixture which comprises 5 to 70 wt % of at least one N-acetylated oligosaccharide, 20 to 90 wt % of at least one neutral galacto-oligosaccharide and 5 to 50 wt % of at least one sialylated oligosaccharide.
Most research interest has focused on the fermentability and bifidogenicity of oligosaccharide prebiotics. However, in vitro studies have shown that a number of oligosaccharide prebiotics mimic the eukaryotic cell surface receptors to which virulent bacteria adhere as part of the pathogenicity process (Shoaf et al, 2006). Further, trans-galacto-oligosaccharides have been found to enhance the protective abilities of Bifidobacterium breve in mice infected with Salmonella enterica (Asahara et al, 2001). Other potential benefits of prebiotics have also been investigated in adults including immunomodulatory properties, bone mineralisation and cardiovascular effects. Studies on neonates and infants have concentrated on the abilities of oligosaccharides to increase faecal Bifidobacteria populations. Surprisingly few studies have been carried out on disease prevention or possible treatment benefits of prebiotic use in infants.
In recent years, concerns about overweight and obesity in the adult population have grown substantially to the point where obesity is the most burdensome and costly nutritional condition worldwide. As a result, attention is starting to focus on the significance of developments during infancy for the risk of obesity later in life with particular regard to the extent to which growth during infancy may be a predictor of later adiposity. Some commentators believe that weight gain in the first six months of life is primarily a gain in fat; if weight gain in infancy is indeed predictive of later adiposity, it follows that gains in adiposity in infancy may need to be carefully monitored to reduce the risk of obesity of the individual later in life (Gilman M. W., “The first months of life: a critical period for development of obesity” Am J Clin Nutr 2008; 87: 1587-9).